The renal medulla (papilla) through its renomedullary interstitial cells (RIC) exerts a non-excretory antihypertensive function. The non-excretory antihypertensive function of the whole kidney, as well as that of the renal papilla, is effective even in the face of a Na-volume load. Therefore, this function appears to mitigate the effect of the "volume component" of the hypertensive state. The action of transplants of fragmented papilla as well as RIC grown in tissue culture as monolayer almost certainly is mediated by a factor(s) that is absorbed and circulates as a hormone. Lipid extracts of cultured RIC when injected parenterally into hypertensive animals duplicate the antihypertensive action of the transplanted cells. This suggests that the antihypertensive agent of the renal papilla is a lipid. From renomedullary tissue two antihypertensive lipid moieties have been extracted and semi-purified. One is polar (ARL-polar) and evokes two effects: a. potent acute depressor effect within about 2 seconds after a intravenous bolus dose (mean arterial pressure from 180 to 100 mm Hg depending on dose) b. a prolonged depressor effect after multiple doses that may remain for 24-48 hours after the last dose. A dose response curve of the acute depressor effect entails both the immediate maximal depression and the duration of the effect (up to hours with larger doses). The other lipid moiety is neutral (ARL-neutral). After an intravenous dose there is a lag of a few minutes (2-6) following which the arterial pressure slowly declines over one to two hours (inclined plane configuration). The return to prior pressure may require one or several hours. Purification of the polar compound has reached the stage where identification is possible. Purification of the neutral compound to this level seems feasible. It is proposed to identify these substances and to determine the mechanism by which these two agents exert their antihypertensive effect.